Study of Ibrutinib in Combination With Bendamustine and Rituximab for Patients With Relapsed/Refractory Aggressive BCL

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02747732
• Date of registration: 20/04/2016
• Prospective Registration: Yes
• Primary sponsor: Meirav Kedmi MD
• Public title: Study of Ibrutinib in Combination With Bendamustine and Rituximab for Patients With Relapsed/Refractory Aggressive BCL
• Scientific title: A Phase II Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Bendamustine and Rituximab (BR) for Patients With Relapsed/Refractory Aggressive B Cell Lymphomas
• Date of first enrolment: December 2016
• Target sample size: 72
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT02747732
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Israel

Contacts

• Name: MEIRAV KEDMI
• Affiliation: Sheba Medical Center

• Name: MEIRAV KEDMI, MD

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Adult patients over the age of 18.

2. Histologically confirmed DLBCL, Transformed low grade lymphoma to DLBCL, primary
mediastinal B cell lymphoma or unclassifiable lymphoma between DLBCL and Burkitt
Lymphoma, either in first or second relapse/progression in patients who are not
candidates for ASCT or in second relapse/progression post ASCT (as first salvage
therapy following relapse/progression post ASCT).

3. Pathology must be confirmed by a local hemato-pathologist. Patients with pathology
sample over 1 year old will have to undergo a new diagnostic biopsy.

4. At least 1 prior line of therapy with rituximab containing regimen.

5. At least 1 site of measurable disease according to the Lugano criteria [1]

6. Hematology laboratory values must be within the following limits:

1. Absolute neutrophil count (ANC)=1000/mm3 independent of growth factor support

2. Platelets =100,000/mm3 or =50,000/mm3 if bone marrow involvement independent of
transfusion support in either situation.

7. Biochemical values within the following limits:

1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x upper
limit of normal (ULN)

2. Total bilirubin = 1.5 x ULN unless the increase is due to Gilbert's syndrome or
of non-hepatic origin

3. Serum creatinine = 2 x ULN or estimated Glomerular Filtration Rate
(Cockroft-Gault) = 40 mL/min/1.73m2

8. Women of childbearing potential and men who are sexually active must be practicing a
highly effective method of birth control during and after the study consistent with
local regulations regarding the use of birth control methods for subjects
participating in clinical trials. Men must agree to not donate sperm during and after
the study. For females, these restrictions apply for 1 month after the last dose of
study drug. For males, these restrictions apply for 3 months after the last dose of
study drug.

9. Women of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [beta-hCG]) or urine pregnancy test at screening. Women who are pregnant
or breastfeeding are ineligible for this study.

10. ECOG performance status 0-2.

11. Sign (or their legally-acceptable representatives must sign) an informed consent
document indicating that they understand the purpose of and procedures required for
the study, including biomarkers, and are willing to participate in the study.

Exclusion Criteria:

Prior chemotherapy radiotherapy or major surgery within 4 weeks of cycle 1 day 1.

2. Previous treatment with either bendamustine or Ibrutinib. 3. Prior allogeneic stem cell
transplantation. 4. Known central nervous system lymphoma. 5. History of stroke or
intracranial hemorrhage within 6 months prior to randomization.

6. Requires anticoagulation with warfarin or equivalent vitamin K antagonists. 7. Requires
treatment with strong CYP3A inhibitors. 8. Clinically significant cardiovascular disease
such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial
infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe)
cardiac disease as defined by the New York Heart Association Functional Classification.

9. Vaccinated with live, attenuated vaccines within 4 weeks of randomization. 10. Known
history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active
Hepatitis B Virus infection or any uncontrolled active systemic infection requiring
intravenous (IV) antibiotics. Hbcore positive HBs negative patients will be eligible but
will need to be treated with lamivudine 100 mg/day throughout the treatment phase and 6
months after it.

11. Any life-threatening illness, medical condition, or organ system dysfunction which, in
the investigator's opinion, could compromise the subject's safety, interfere with the
absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.

12. Diagnosed or treated for malignancy other than DLBCL, except:

1. Malignancy treated with curative intent and with no known active disease present for 3
years before randomization

2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
disease

3. Adequately treated carcinoma in situ without evidence of disease



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Transformed Indolent Lymphoma

Primary Mediastinal (Thymic) Large B-cell Lymphoma

Refractory Cancer

Recurrent Disease

Diffuse Large B Cell Lymphoma

Intervention(s)

Drug: Bendamustine 90 mg/m2 IV on Days 1-2, Cycles 1-6

Primary Outcome(s)

overall response rate (ORR) of the combination of ibrutinib, bendamustine and rituximab (IBR) [Time Frame: 5 years]

Secondary Outcome(s)

progression free survival (PFS) [Time Frame: 5 years]

overall survival (OS) [Time Frame: 5 years]

duration of response. [Time Frame: 5 years]

Secondary ID(s)

Bruton's Tyrosine_Meirav Kedmi

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Johnson & Johnson